Selective relay of afferent sensory-induced action potentials from peripheral nerve to brain and the effects of electrical stimulation

Electrical stimulation of peripheral nerve fibers and dorsal column fibers is used to treat acute and chronic pain. Recent studies have shown that sensitized A-fibers maybe involved in the relay of pain information. These nerve fibers also carry sensory-induced action potentials (APs), such as proprioception, mechanoreception, etc. Electrical stimulation of these nerve fibers can result in interactions between sensory-induced APs and stimulation-induced APs. For example, the sensory-induced APs can collide with stimulus APs, and thus may never be relayed to the brain. In this study, we aimed to quantify the effects of stimulation frequency on these interactions. Specifically, we focused on the goal of stimulation to simultaneously (i) block noxious sensory signals while (ii) relaying innocuous sensory signals from the periphery to the brain via a myelinated nerve fiber. We defined a performance metric called the 'selective relay (SR) ' measure. Specifically, we constructed a tractable model of a nerve fiber that receives two inputs: the underlying sensory activity at the bottom of the fiber (noxious or innocuous), and the external stimulus applied to the middle of the fiber. We then defined relay reliability, R, as the percentage of sensory APs that make it to the top of the fiber. SR is then a product of relaying innocuous sensory information while blocking noxious pain stimuli, i.e., SR=R_sen (1-R_pain). We applied the two inputs to the fiber at various frequencies and analyzed relay reliability and then we studied selective relay assuming noxious and innocuous stimuli produce APs with distinct frequencies. We found that frequency stimulation between 50-100Hz effectively blocks relay of low-frequency pain signals, allowing mid-to-high frequency sensory signals to transmit to the brain.